EP0990655B1 - Method for drying anhydrous paroxetine hydrochloride - Google Patents
Method for drying anhydrous paroxetine hydrochloride Download PDFInfo
- Publication number
- EP0990655B1 EP0990655B1 EP99945685A EP99945685A EP0990655B1 EP 0990655 B1 EP0990655 B1 EP 0990655B1 EP 99945685 A EP99945685 A EP 99945685A EP 99945685 A EP99945685 A EP 99945685A EP 0990655 B1 EP0990655 B1 EP 0990655B1
- Authority
- EP
- European Patent Office
- Prior art keywords
- paroxetine hydrochloride
- isopropyl alcohol
- hydrochloride anhydrate
- drying
- weight
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- AHOUBRCZNHFOSL-UHFFFAOYSA-N 3-(1,3-benzodioxol-5-yloxymethyl)-4-(4-fluorophenyl)piperidine Chemical compound C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 title claims abstract description 239
- 229960005183 paroxetine hydrochloride Drugs 0.000 title claims abstract description 112
- 238000001035 drying Methods 0.000 title claims abstract description 71
- 238000000034 method Methods 0.000 title claims abstract description 36
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims abstract description 299
- 229960002296 paroxetine Drugs 0.000 claims abstract description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 12
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims abstract description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- AHOUBRCZNHFOSL-YOEHRIQHSA-N (+)-Casbol Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-N 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 3
- -1 paroxetine compound Chemical class 0.000 abstract description 10
- 239000013078 crystal Substances 0.000 description 67
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 14
- 239000001569 carbon dioxide Substances 0.000 description 7
- 229910002092 carbon dioxide Inorganic materials 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 230000000052 comparative effect Effects 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
- 230000007547 defect Effects 0.000 description 5
- 229910001873 dinitrogen Inorganic materials 0.000 description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- 238000004566 IR spectroscopy Methods 0.000 description 4
- 238000002441 X-ray diffraction Methods 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 238000001291 vacuum drying Methods 0.000 description 4
- 238000001914 filtration Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000004904 shortening Methods 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 239000000935 antidepressant agent Substances 0.000 description 2
- 229940005513 antidepressants Drugs 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 239000011261 inert gas Substances 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000011085 pressure filtration Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
Definitions
- the present invention relates to a process for drying paroxetine hydrochloride anhydrate. More specifically, the present invention relates to a process for drying paroxetine hydrochloride anhydrate to reduce the amount of remaining isopropyl alcohol.
- Paroxetine hydrochlorides such as paroxetine hydrochloride anhydrate are useful compounds as antidepressants.
- paroxetine hydrochloride anhydrate obtained by reacting paroxetine with hydrogen chloride in the presence of isopropyl alcohol contains isopropyl alcohol. Therefore, in order not to deform its crystal form, the paroxetine hydrochloride anhydrate is dried by a vacuum drying process employing a vacuum oven which is temperature-adjusted to a temperature lower than 80°C.
- EP-A-0 812 827 relates to intermediates suitable for the preparation of paroxetine and the preparation of paroxetine hydrochloride therefrom. According to one experiment, paroxetine hydrochloride is crystallized from isopropanol washed with cold isopropanol and dried under reduced pressure at 70°C to give paroxetine hydrochloride containing 10.6% isopropanol.
- the experiment then investigated the further drying of the product at temperatures of 70°C, 80°C, 90°C, 100°C and 110°C for varying time periods up to 168 hours and concluded that by the combination of drying temperatures ranging from 80°C to 110°C and a drying time up to 168 hours, the amount of residual isopropanol can be controlled in the range 0.1 to 5%.
- An object of the present invention is to provide a process for drying paroxetine hydrochloride anhydrate capable of efficiently reducing the amount of remaining isopropyl alcohol in the paroxetine hydrochloride anhydrate, which is obtained by crystallizing in the presence of isopropyl alcohol, without the necessity of a large-scaled apparatus.
- the present invention provides a process for drying paroxetine hydrochloride anhydrate comprising:
- the present invention also provides a process for the production of paroxetine hydrochloride anhydrate comprising:
- the paroxetine hydrochloride anhydrate can be obtained by, for instance, a process comprising dissolving a paroxetine compound (paroxetine or N-tert-butoxycarbonylparoxetine) in isopropyl alcohol, and thereafter reacting the paroxetine compound with hydrogen chloride, whereby reacting the paroxetine compound with hydrogen chloride in the presence of isopropyl alcohol; and crystallizing the resulting product.
- This paroxetine hydrochloride anhydrate usually contains 30 to 70% by weight or so of isopropyl alcohol.
- N-tert-butoxycarbonylparoxetine is (3S, 4R)-trans-1-tert-butoxycarbonyl-4-(4-fluorophenyl)-3-[3, 4-methylenedioxyphenyl) oxymethyl]piperidine.
- the amount of hydrogen chloride used in the reaction with the paroxetine compound is usually 1 to 5 mol or so per 1 mol of the paroxetine compound.
- the amount of paroxetine compound is not limited to specified ones. It is preferable that the amount of the paroxetine hydrochloride anhydrate is 5 to 60 parts by weight, based on 100 parts by weight of isopropyl alcohol.
- the reaction temperature of the paroxetine compound with hydrogen chloride may be usually within the range of ambient temperature to the boiling point of isopropyl alcohol.
- isopropyl alcohol may be used alone, or used in combination with, for instance, other organic solvents, organic acids, and the like in an amount which would not hinder the object of the present invention.
- water is not contained in isopropyl alcohol from the viewpoint of shortening the drying time. Therefore, it is preferable that isopropyl alcohol is substantially non-water-containing isopropyl alcohol, i.e. one having a water content of not more than 0.1%.
- the reaction time is not limited to specified ones.
- the reaction time can be usually up to the termination of the reaction.
- reaction solution of the formed paroxetine hydrochloride anhydrate impurities are contained in some cases.
- the reaction solution in order to remove the impurities, can be treated with activated charcoal.
- isopropyl alcohol is contained in the crystals of the resulting paroxetine hydrochloride anhydrate.
- the crystals of paroxetine hydrochloride anhydrate containing isopropyl alcohol are extremely thermally unstable. For instance, when the crystals of paroxetine hydrochloride anhydrate containing isopropyl alcohol are dried at a temperature of not less than 80°C, a portion of the crystals of paroxetine hydrochloride anhydrate is dissolved in the isopropyl alcohol contained, and thereby its crystal form is deformed, so that a desired crystal form cannot be obtained [see Comparative Example 2 described below].
- this paroxetine hydrochloride anhydrate containing isopropyl alcohol is dried at a temperature of not more than 60°C and under normal pressure or lower in an atmosphere which does not substantially contain moisture until the content of isopropyl alcohol attains to not more than 15% by weight.
- the first drying step of the present invention is carried out in an atmosphere of which relative humidity (at 20°C) is not more than 10%, preferably not more than 5%.
- This atmosphere includes, for instance, dried air, and inert gases such as nitrogen gas and argon gas.
- the inert gases such as nitrogen gas and argon gas are preferable because they can easily form an atmosphere of which relative humidity (at 20°C) is not more than 10%.
- the pressure of the atmosphere may be normal pressure or lower.
- a drying process there can be employed a process for drying in an open system such as through-flow drying and a process for drying in a closed system such as drying under reduced pressure.
- the pressure inside the system is adjusted to a reduced pressure of not more than 200 mm Hg, preferably not more than 100 mm Hg, more preferably not more than 50 mm Hg, from the viewpoint of improving drying efficiency.
- the temperature in the course of drying the paroxetine hydrochloride anhydrate is not more than 60°C, preferably not more than 50°C, from the viewpoint of maintaining the crystal form of the paroxetine hydrochloride anhydrate. It is desired that the temperature is not less than 15°C, preferably not less than 20°C, from the viewpoint of improving drying efficiency.
- the drying of the paroxetine hydrochloride anhydrate is carried out until the content of the isopropyl alcohol in the paroxetine hydrochloride anhydrate attains to not more than 15% by weight, preferably not more than 13% by weight.
- the lower limit of the content of isopropyl alcohol after drying is not limited to specified ones.
- the subsequent heating and drying procedures are carried out at a stage where the content of isopropyl alcohol attains to 8 to 15% by weight or so, from the viewpoint of shortening the time period necessary for drying.
- the content of isopropyl alcohol in the paroxetine hydrochloride anhydrate in the course of carrying out the drying procedures can be confirmed by, for instance, gas chromatography, nuclear magnetic resonance spectroscopy (NMR), or the like.
- the paroxetine hydrochloride anhydrate After drying is carried out until the content of isopropyl alcohol in the paroxetine hydrochloride anhydrate attains to not more than 15% by weight, the paroxetine hydrochloride anhydrate is further dried at a temperature of 80° to 110°C until the content of isopropyl alcohol attains to 5% by weight in an atmosphere reduced to not more than 20 mm Hg.
- one of the features of the present invention also resides in that a drying procedure is carried out as a secondary step subsequently to the above drying procedure as a first step.
- the paroxetine hydrochloride anhydrate is deformed in the crystal form at a temperature of not less than 80°C.
- desired crystals of the paroxetine hydrochloride anhydrate can be obtained without the deformation of its crystal form, nevertheless drying is carried out at a temperature of more than 80°C, which cannot be expected from the conventional techniques.
- isopropyl alcohol is present on the surface of the crystals of the paroxetine hydrochloride anhydrate in an amount of about 20 to about 60% by weight based on the weight of the paroxetine hydrochloride anhydrate, and isopropyl alcohol is incorporated into the inside of the crystals in an amount of about 10 to about 15% by weight based on the weight of the paroxetine hydrochloride anhydrate.
- isopropyl alcohol is present on the surface of the crystals of the paroxetine hydrochloride anhydrate in an amount of about 20 to about 60% by weight based on the weight of the paroxetine hydrochloride anhydrate
- isopropyl alcohol is incorporated into the inside of the crystals in an amount of about 10 to about 15% by weight based on the weight of the paroxetine hydrochloride anhydrate.
- isopropyl alcohol existing on its surface is removed because the drying procedure is employed in the first step.
- isopropyl alcohol existing on the surface is previously removed, even when the paroxetine hydrochloride anhydrate is heated to a temperature of not less than 80°C at which its crystal form is thought to be deformed, it is thought that the drying of the crystals can be efficiently carried out without causing the deformation of the crystals by the dissolution of the crystals in isopropyl alcohol.
- the object of the present invention cannot be achieved by simply heating the crystals to a temperature of not less than of 80°C to remove isopropyl alcohol incorporated in the crystals.
- drying can be efficiently carried out because the drying procedure in the second step is carried out in an atmosphere reduced to not more than 20 mm Hg, isopropyl alcohol is sequentially efficiently discharged from the inside of the crystal to its outside.
- the temperature of the atmosphere is adjusted to a temperature of 80° to 110°C, and thereafter the atmosphere may be reduced to not more than 20 mm Hg.
- the atmosphere is reduced to not more than 20 mm Hg, and thereafter the temperature of the atmosphere may be adjusted to a temperature of 80° to 110°C.
- the temperature may be raised in multi-steps or continuously.
- the temperature in the course of drying the paroxetine hydrochloride anhydrate is not less than 80°C, preferably not less than 90°C, from the viewpoint of the improvement of the drying efficiency, and the temperature is not more than 110°C, preferably not more than 100°C, in consideration that the melting point of the paroxetine hydrochloride anhydrate is 115° to 120°C.
- the pressure of the atmosphere in the course of drying the paroxetine hydrochloride anhydrate is as low as possible, from the viewpoint of the shortening the drying time and maintaining the crystal form. From the above aspects, the pressure of the atmosphere is not more than 20 mm Hg, preferably not more than 10 mm Hg.
- the drying procedure in the first step and the drying procedure in the second step are continuously carried out in the same system in order to efficiently carry out the drying.
- the content of isopropyl alcohol in the paroxetine hydrochloride anhydrate is not less than 2.0% by weight, preferably not less than 2.3% by weight, more preferably 2.5% by weight.
- the activated charcoal was removed from the solution at a temperature of about 70°C by filtration, and thereafter the resulting filtrate was gradually cooled to 0° to 5°C.
- the mixture was additionally stirred at a temperature of 0° to 5°C for 1 hour, and the paroxetine hydrochloride anhydrate was allowed to precipitate, and the precipitate was collected by filtration under nitrogen gas stream.
- the resulting crystals of the paroxetine hydrochloride anhydrate contained 53.5% by weight of isopropyl alcohol.
- paroxetine hydrochloride anhydrate containing 53.5% by weight of isopropyl alcohol, obtained in Preparation Example 1 was dried at room temperature (about 20°C) under reduced pressure of 2 to 20 mm Hg for 12 hours to adjust the content of isopropyl alcohol to 9.8% by weight.
- the crystals of the paroxetine hydrochloride anhydrate containing 53.5% by weight of isopropyl alcohol, obtained in Preparation Example 1 were dried at room temperature (about 20°C) in nitrogen gas stream [relative humidity (20°C): 0.1%] for 24 hours. As a result, the content of isopropyl alcohol in the crystals of the paroxetine hydrochloride anhydrate was 12.6% by weight.
- the crystals of the paroxetine hydrochloride anhydrate were dried at 80°C for 18 hours under reduced pressure of 1 to 3 mm Hg, to give crystals of the paroxetine hydrochloride anhydrate containing 2.9% by weight of isopropyl alcohol.
- the crystal form of the resulting paroxetine hydrochloride anhydrate was examined by powdered X-ray diffraction and infrared absorption spectroscopy. However, no deformation was found.
- paroxetine hydrochloride anhydrate was prepared in the same manner as in Preparation Example 1, to give 1423.5 g of crystals of paroxetine hydrochloride anhydrate.
- the crystals contained 59.3% by weight of isopropyl alcohol.
- the crystals of the paroxetine hydrochloride anhydrate containing isopropyl alcohol were dried at a temperature of 50° to 60°C and under reduced pressure of 3 to 150 mm Hg.
- the content of isopropyl alcohol in the crystals of the paroxetine hydrochloride anhydrate was 10.8% by weight.
- the paroxetine hydrochloride anhydrate was prepared in the same manner as in Preparation Example 1, and thereafter an isopropyl alcohol solution containing the crystals of the paroxetine hydrochloride anhydrate was subjected to pressure filtration by nitrogen gas with a pressure filter (Druck filter). The resulting 26.0 kg of the crystals of paroxetine hydrochloride anhydrate contained 58.5% by weight of isopropyl alcohol.
- the crystals of paroxetine hydrochloride anhydrate containing 58.5% by weight of isopropyl alcohol were dried in the pressure filter at the temperature of 50°C and under reduced pressure of 10 to 80 mm Hg, and the content of isopropyl alcohol was adjusted to 13.1% by weight.
- drying was further carried out for about 12 hours under reduced pressure of 1 to 3 mm Hg, with adjusting the temperature of the crystals of paroxetine hydrochloride anhydrate to 85°C to dry the crystals of paroxetine hydrochloride anhydrate.
- the content of isopropyl alcohol in the dried crystals was 2.3% by weight.
- the crystal form of the paroxetine hydrochloride anhydrate was examined by powdered X-ray diffraction and infrared absorption spectroscopy. However, no deformation was found.
- Example 2 The crystals containing 12.6% by weight of isopropyl alcohol obtained in Example 2 were dried for the same period of time as in Example 2, i.e. 18 hours, under reduced pressure of 1 to 3 mm Hg and at 70°C. However, the content of isopropyl alcohol was 9.6% by weight.
- the paroxetine hydrochloride anhydrate containing 53.5% by weight of isopropyl alcohol obtained in Example 1 was dried for 13 hours at 90°C under reduced pressure of 54 to 85 mm Hg. As a result, a part of the crystals was melted, and its crystal form was deformed.
- the resulting crystals were subjected to IR analysis to determine its water amount. As a result, the crystals were found to be paroxetine hydrochloride hemihydrate.
- paroxetine hydrochloride anhydrate of the present invention there can be exhibited an excellent effect that the amount of remaining isopropyl alcohol contained in the paroxetine hydrochloride anhydrate can be efficiently reduced in a short period of time without using a large-scaled apparatus.
- paroxetine hydrochloride anhydrate obtained by the process of the present invention can be suitably used as intermediates for antidepressants.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Psychiatry (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pain & Pain Management (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10105898A JP3796351B2 (ja) | 1998-04-13 | 1998-04-13 | パロキセチン塩酸塩無水和物の乾燥方法 |
| JP10105898 | 1998-04-13 | ||
| PCT/JP1999/001914 WO1999052902A1 (en) | 1998-04-13 | 1999-04-12 | Method for drying anhydrous paroxetine hydrochloride |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| EP0990655A1 EP0990655A1 (en) | 2000-04-05 |
| EP0990655A4 EP0990655A4 (en) | 2001-10-04 |
| EP0990655B1 true EP0990655B1 (en) | 2003-07-02 |
Family
ID=14290525
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP99945685A Expired - Lifetime EP0990655B1 (en) | 1998-04-13 | 1999-04-12 | Method for drying anhydrous paroxetine hydrochloride |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US6541637B1 (enExample) |
| EP (1) | EP0990655B1 (enExample) |
| JP (1) | JP3796351B2 (enExample) |
| AT (1) | ATE244237T1 (enExample) |
| AU (1) | AU730652B2 (enExample) |
| CA (1) | CA2294716C (enExample) |
| DE (1) | DE69909207T2 (enExample) |
| ES (1) | ES2199592T3 (enExample) |
| PT (1) | PT990655E (enExample) |
| WO (1) | WO1999052902A1 (enExample) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1394160A1 (en) | 1996-06-13 | 2004-03-03 | SUMIKA FINE CHEMICALS Co., Ltd. | Process for preparing crystalline paroxetin hydrochloride |
| DK1100796T3 (da) * | 1998-08-07 | 2003-08-25 | Smithkline Beecham Plc | Fremgangsmåde til fremstilling af en ikke-krystallinsk anhydratform af paroxetinhydrochlorid |
| GB9826176D0 (en) * | 1998-11-28 | 1999-01-20 | Smithkline Beecham Plc | Novel process |
| US20080033050A1 (en) * | 2006-08-04 | 2008-02-07 | Richards Patricia Allison Tewe | Method of treating thermoregulatory disfunction with paroxetine |
| US9138430B2 (en) * | 2007-12-27 | 2015-09-22 | Mylan Specialty L.P. | Formulation and method for the release of paroxetine in the large intestine |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SK283608B6 (sk) | 1995-02-06 | 2003-10-07 | Smithkline Beecham Plc | Bezvodý hydrochlorid paroxetínu, spôsob jeho výroby a použitie |
| US5856493A (en) * | 1995-02-06 | 1999-01-05 | Smithkline Beecham Corporation | Process for making novel form of paroxeting hydrochloride anhydrate |
| EP1394160A1 (en) * | 1996-06-13 | 2004-03-03 | SUMIKA FINE CHEMICALS Co., Ltd. | Process for preparing crystalline paroxetin hydrochloride |
| JP3819532B2 (ja) | 1996-06-13 | 2006-09-13 | 住友化学株式会社 | ピペリジン誘導体およびその製造方法 |
| DK1100796T3 (da) * | 1998-08-07 | 2003-08-25 | Smithkline Beecham Plc | Fremgangsmåde til fremstilling af en ikke-krystallinsk anhydratform af paroxetinhydrochlorid |
-
1998
- 1998-04-13 JP JP10105898A patent/JP3796351B2/ja not_active Expired - Fee Related
-
1999
- 1999-04-12 ES ES99945685T patent/ES2199592T3/es not_active Expired - Lifetime
- 1999-04-12 DE DE69909207T patent/DE69909207T2/de not_active Expired - Lifetime
- 1999-04-12 CA CA002294716A patent/CA2294716C/en not_active Expired - Fee Related
- 1999-04-12 AU AU52656/99A patent/AU730652B2/en not_active Ceased
- 1999-04-12 PT PT99945685T patent/PT990655E/pt unknown
- 1999-04-12 WO PCT/JP1999/001914 patent/WO1999052902A1/ja not_active Ceased
- 1999-04-12 EP EP99945685A patent/EP0990655B1/en not_active Expired - Lifetime
- 1999-04-12 AT AT99945685T patent/ATE244237T1/de active
- 1999-04-12 US US09/445,598 patent/US6541637B1/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| EP0990655A1 (en) | 2000-04-05 |
| JP2001072677A (ja) | 2001-03-21 |
| EP0990655A4 (en) | 2001-10-04 |
| PT990655E (pt) | 2003-11-28 |
| CA2294716A1 (en) | 1999-10-21 |
| ES2199592T3 (es) | 2004-02-16 |
| ATE244237T1 (de) | 2003-07-15 |
| AU730652B2 (en) | 2001-03-08 |
| DE69909207D1 (de) | 2003-08-07 |
| JP3796351B2 (ja) | 2006-07-12 |
| CA2294716C (en) | 2004-08-03 |
| DE69909207T2 (de) | 2004-04-22 |
| AU5265699A (en) | 1999-11-01 |
| WO1999052902A1 (en) | 1999-10-21 |
| US6541637B1 (en) | 2003-04-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2161609C2 (ru) | Способ получения высокочистого меламина | |
| CA2538265C (en) | Process for producing imide compound | |
| NO340220B1 (no) | Krystallinsk glykopyrroniumbromid | |
| CA2513951C (en) | Method for the production of d-threo-2-phenyl-2-piperidine-2-yl acetate | |
| EP0990655B1 (en) | Method for drying anhydrous paroxetine hydrochloride | |
| US5057615A (en) | Process for purifying tryptophan | |
| NO309266B1 (no) | Fremgangsmåte for fremstilling av optisk anriket bupivacain | |
| US20100174085A1 (en) | crystalline polymorphic forms of fexofenadine | |
| AU2001278094B2 (en) | Novel crystalline forms of 4-[4-[4-(hydroxydiphenylmethyl)-1-piperindinyl]-1-hydroxybutyl]-alpha, alpha-dimethylbenzene acetic acid and its hydrochloride | |
| NO322795B1 (no) | Fremgangsmate for fremstilling av iohexol | |
| SK179097A3 (en) | Process for the production of enantiomerically-pure azetidine-2-carboxylic acid | |
| EP2457899A1 (en) | Process for production of optically active nipecotamide | |
| US5470988A (en) | Process for the preparation of purified phthalimidoalkanecarboxylic acids | |
| US20020151716A1 (en) | Process for the production of paroxetine | |
| KR100469030B1 (ko) | 시사프라이드의 합성방법 | |
| KR100575020B1 (ko) | 멜라민의 정제방법 | |
| AU2005263761A1 (en) | Improved process for the manufacture of mirtazapine | |
| KR100491479B1 (ko) | 제미플록사신 메실레이트의 향상된 건조 및 흡습 방법 | |
| JPH07278154A (ja) | ヒドロキシフェニルプロピオン酸エステルの製造法 | |
| EP0552019A2 (en) | Method of producing 1,4-dihydroxy-2-naphthoic acid | |
| MXPA06001128A (en) | Process for producing imide compound | |
| EP1178962A1 (en) | Process for the preparation of paroxetine acetate and analogues thereof | |
| JP2003104934A (ja) | フマル酸及び／又はリンゴ酸の製造方法 | |
| JPWO1997043256A1 (ja) | ３−ヒドロキシピロリジンの製造法 | |
| MXPA97008494A (en) | New process for the preparation of clorhidratode ropivacain monohidrat |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
| 17P | Request for examination filed |
Effective date: 19991213 |
|
| AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE CH DE ES FR GB IT LI PT |
|
| A4 | Supplementary search report drawn up and despatched |
Effective date: 20010817 |
|
| AK | Designated contracting states |
Kind code of ref document: A4 Designated state(s): AT BE CH DE ES FR GB IT LI PT |
|
| 17Q | First examination report despatched |
Effective date: 20020102 |
|
| GRAH | Despatch of communication of intention to grant a patent |
Free format text: ORIGINAL CODE: EPIDOS IGRA |
|
| GRAH | Despatch of communication of intention to grant a patent |
Free format text: ORIGINAL CODE: EPIDOS IGRA |
|
| GRAA | (expected) grant |
Free format text: ORIGINAL CODE: 0009210 |
|
| AK | Designated contracting states |
Designated state(s): AT BE CH DE ES FR GB IT LI PT |
|
| REG | Reference to a national code |
Ref country code: GB Ref legal event code: FG4D |
|
| REG | Reference to a national code |
Ref country code: CH Ref legal event code: EP |
|
| REF | Corresponds to: |
Ref document number: 69909207 Country of ref document: DE Date of ref document: 20030807 Kind code of ref document: P |
|
| REG | Reference to a national code |
Ref country code: CH Ref legal event code: NV Representative=s name: MOINAS & SAVOYE SA |
|
| REG | Reference to a national code |
Ref country code: ES Ref legal event code: FG2A Ref document number: 2199592 Country of ref document: ES Kind code of ref document: T3 |
|
| ET | Fr: translation filed | ||
| PLBE | No opposition filed within time limit |
Free format text: ORIGINAL CODE: 0009261 |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT |
|
| 26N | No opposition filed |
Effective date: 20040405 |
|
| REG | Reference to a national code |
Ref country code: FR Ref legal event code: TP |
|
| REG | Reference to a national code |
Ref country code: GB Ref legal event code: 732E |
|
| REG | Reference to a national code |
Ref country code: CH Ref legal event code: PUE Owner name: SUMITOMO CHEMICAL COMPANY, LIMITED Free format text: SUMIKA FINE CHEMICALS CO., LTD.#1-21, UTAJIMA-3-CHOME, NISHIYODOGAWA-KU#OSAKA-SHI, OSAKA 555-0021 (JP) -TRANSFER TO- SUMITOMO CHEMICAL COMPANY, LIMITED#5-33, KITAHAMA 4-CHOME CHUO-KU#OSAKA (JP) |
|
| REG | Reference to a national code |
Ref country code: PT Ref legal event code: PC4A Owner name: SUMITOMO CHEMICAL COMPANY, LIMITED, JP Effective date: 20041130 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: PT Payment date: 20110324 Year of fee payment: 13 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: CH Payment date: 20110412 Year of fee payment: 13 Ref country code: DE Payment date: 20110406 Year of fee payment: 13 Ref country code: ES Payment date: 20110518 Year of fee payment: 13 Ref country code: FR Payment date: 20110426 Year of fee payment: 13 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: AT Payment date: 20110328 Year of fee payment: 13 Ref country code: BE Payment date: 20110411 Year of fee payment: 13 Ref country code: GB Payment date: 20110406 Year of fee payment: 13 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: IT Payment date: 20110412 Year of fee payment: 13 |
|
| REG | Reference to a national code |
Ref country code: PT Ref legal event code: MM4A Free format text: LAPSE DUE TO NON-PAYMENT OF FEES Effective date: 20121012 |
|
| BERE | Be: lapsed |
Owner name: *SUMITOMO CHEMICAL COMPANY LTD Effective date: 20120430 |
|
| REG | Reference to a national code |
Ref country code: CH Ref legal event code: PL |
|
| REG | Reference to a national code |
Ref country code: AT Ref legal event code: MM01 Ref document number: 244237 Country of ref document: AT Kind code of ref document: T Effective date: 20120412 |
|
| GBPC | Gb: european patent ceased through non-payment of renewal fee |
Effective date: 20120412 |
|
| REG | Reference to a national code |
Ref country code: FR Ref legal event code: ST Effective date: 20121228 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: LI Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20120430 Ref country code: GB Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20120412 Ref country code: BE Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20120430 Ref country code: CH Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20120430 Ref country code: AT Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20120412 |
|
| REG | Reference to a national code |
Ref country code: DE Ref legal event code: R119 Ref document number: 69909207 Country of ref document: DE Effective date: 20121101 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: FR Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20120430 Ref country code: IT Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20120412 Ref country code: PT Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20121012 |
|
| REG | Reference to a national code |
Ref country code: ES Ref legal event code: FD2A Effective date: 20130715 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: ES Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20120413 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: DE Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20121101 |